Disease Progression without PSA Rise in Patients with Metastatic Castration-Resistant Prostate Cancer

Chicago—Results from recent studies have demonstrated the high frequency with which metastatic prostate cancer can progress either radiographically or symptomatically without a rise in prostate-specific antigen (PSA), an occurrence known as PSA-clinical discordance. According to Alan Haruo Bryce, MD, and colleagues, “recognizing this clinical phenomenon is important to implementing appropriate criteria for disease monitoring during treatment.”

The researchers conducted a study that included 790 men who were accrued from July 28, 2006, to November 21, 2012. Results of the study were reported during a poster session at the ASCO 2018 Annual Meeting in a poster titled Patterns of PSA versus Clinically Progressive Disease in the E3805 CHAARTED Trial.

The 790 participants were randomized to receive androgen deprivation therapy (ADT) alone or ADT plus docetaxel at 75 mg/m2 every 3 weeks for six cycles. The men were prospectively stratified into high volume versus low volume disease. Clinically progressive disease was defined as increase in symptomatic bone metastases, progression per Response Evaluation Criteria in Solid Tumors criteria, or clinical deterioration associated with cancer per the investigator’s opinion. PSA progressive disease was defined as an increase in PSA of >50% above the on-treatment nadir, with two consecutive increases a minimum of 2 weeks apart. Concurrent PSA progressive disease and clinically progressing disease is defined as both events occurring within 1 month.

Data cutoff occurred April 30, 2016. As of that point, 403 men with high volume disease and 157 with low volume disease  had progressed. Among the group with high volume disease, the most common pattern of progression was PSA progressive disease, followed by clinically progressive disease; the pattern was common in both the ADT plus docetaxel arm and the ADT alone arm (39.5% vs 43.2%). Clinically progressive disease without PSA progression occurred in 29.5% and 31.0% of patients in the ADT plus docetaxel arm and ADT alone arm, respectively.

In men with low volume disease, clinical disease progression without PSA progression was the dominant pattern of progression, occurring in 44.8% and 34.4% of patients in the ADT plus docetaxel arm and ADT alone arm, respectively.

“Clinical progression of disease in the absence of PSA rise is frequent in patients treated for metastatic castration sensitive prostate cancer. The results highlight the need to incorporate imaging into treatment monitoring rather than relying on PSA alone to trigger imaging,” the researchers said.

Clinical trial information: NCT00309985

Source: Bryce AH, Chen Y-H, Liu G, et al. Patterns of PSA versus clinically progressive disease in the E3805 CHAARTED trial. Abstract of a poster presented at the American Society of Clinical Oncology 2018 Annual Meeting, June 2, 2018, Chicago, Illinois.